POS0787 THE EFFECT OF ANTI-RIBOSOMAL-P AND ANTI-NR2 ANTIBODIES ON FUNCTIONAL BRAIN MRI NETWORKS IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS WITH DEPRESSION AND BEHAVIORAL COGNITIVE DISORDERS.
Authors: E. Chessa, M. Piga, M. Porcu, E. Pintus, A. Perra, C. Serafini, A. Floris, M. Congia, M. M. Angioni, M. G. Carta, L. Saba, A. Mathieu, A. Cauli
Journal: Annals of the Rheumatic Diseases (2022)

Background Cognitive dysfunction (CD) and mood disorders (MD) are among the most frequent neuropsychiatric (NP) events in Systemic Lupus Erythematosus (SLE), but their pathogenesis has not been clarified yet. Until now, an unquestionable correlation between the presence of specific autoantibodies, brain alterations and the presence of CDs and MDs in SLE is lacking. Objectives The primary aim of the study was to explore the effects of anti-NR2 (anti-DWEYS) and anti-ribosomal-P (anti-P) antibodies on CDs and MDs and their relation with functional brain connectivity in patients affected by SLE. Methods A cross-sectional study was conducted, between April 2019 and February 2020, including adult patients who fulfilled the ACR/EULAR 2019 SLE criteria. Demographics, ongoing medications, SLEDAI and SLICC/Damage Index were recorded. Serum level quantification for anti-P (normal values &lt;18 U/ml) and anti-NR2 (normal values &lt;0.5 OD) antibodies were performed using an ELISA. A battery of neuropsychological testing was interpreted by a neuropsychologist, exploring cognitive domains, depression and quality of life. A resting-state functional connectivity (rs-fc) MRI analysis was performed within 2 weeks since the neuropsychological status assessments. Two region of interest to region of interest (ROI-to-ROI) analyses with the graph theory was performed. Results Thirty-three SLE patients (9% male) were enrolled, mean age 43.5 (+-14) years, and median disease duration of 10.4 years (IQR 2.9-25.4) (Table 1). Anti-P were positive (range 0-255 U/ml) in 6 patients (18.2%) and anti-DWEYS (range 0-1.8 OD) in 14 (42.4%). Nineteen out of 33 patients (57.6%) showed at least a cognitive test alteration, but no significant association with antibodies was found. Depression was found in 14 (42.4%) patients using the Center for Epidemiologic Studies Depression Scale (CES-D) as screening instrument. In multiple regression backward models, after correction for age, disease duration, SLEDAI and SDI, the CES-D showed an independent association with anti-P titre (β= 0.32 per U/ml; p=0.049) and prednisone daily dose (β=0.38 per mg/day; p=0.023). The rs-fc MRI analysis revealed a statistically significant association between the titre of anti-P and many altered properties of the brain ROIs (Figure 1), but no effects of PDN daily dose on specific cerebral networks. Table 1. Demographic and clinical characteristics of the patients in total, Legend: PDN: Prednisone; LLDAS: Lupus Low Disease Activity State; OD: Optical density Demographic and clinical characteristics of the participants (N=33) Age, years mean (DS) 43.5 (14.0) Gender (M, %) 3 (9%) Disease duration, months median (IQR) 124.4 (34.7-305) SLEDAI-2k mediane (IQR) 4 (0-14) Dose PDN mg/daily median (IQR) 6.4 (3.8-13.5) LLDAS N, % 12 (36,4%) SLICC-DI mediane (IQR) 0 (0-1) Ongoing treatment 25 (75.8%) Hydroxychloroquine 30 (90.9%) Immunosuppressive 9 (27.3%) Biologics Education less than 8 years 13 (39.4%) Anti-Rib-P N, % 6 (18.2%) Anti-Rib-P (U/ml) mean (DS) 10.9 (5.7-13.3) Anti-DWEYS N, % 14 (42.4%) Anti-DWEYS (OD) mean (DS) 0.4 (0.25-0.67) Anti-phospholipids N, % 11 (33.3%) anti-dsDNA N, % 18 (54.5%) anti-dsDNA Titre mediane (IQR) 22.5 (2.9-74.5) Figure 1. Results of rs-fc MR Analysis 1 (effects of Anti-rib-P titre) on cerebral networks. The regions with decreased and increased property are shown in blue and red nodes, respectively (p&lt; 0.01). The node size represents the significance of the between-group differences in the nodal degree. Conclusion Anti-P antibodies are associated with depressive symptoms and changes of brain network properties in SLE patients, which add knowledge on their pathogenetic effect. Disclosure of Interests None declared